To advance neurological gene therapy applications into the clinic there is an urgent need to improve our understanding of gene delivery vectors, with particular emphasis on distribution and safety after direct brain delivery. While AAV2 currently dominates clinical development, alternative AAV serotypes may be better suited for some applications. The recent game-changing development of image-guided delivery techniques provides opportunity to accurately compare different vectors after direct brain delivery. Accordingly we aim to investigate the distribution and immune responses of 5 AAV serotypes (AAV1, 2, 5, 8 and 9) after confined delivery to grey or white matter structures in the non-human primate (NHP) brain. This in-depth assessment of AAV vectors will provide investigators with scientific rational for selecting a specific vector for a particular neurological application. PUBLIC HEALTH RELEVANCE: Neurological gene delivery is emerging as a viable therapeutic platform with over 200 patients having been treated in clinical trials to date. However, lack of a reliable delivery system has been a major barrier that we have only recently overcome with the development of a complete system for direct image guided brain infusions. This standardized delivery system now enables us to fully investigate alternative gene delivery approaches and will ultimately provide other investigators with the ability to select the best approach for treating a specific neurological disorder.